Gonadotropin Releasing Hormone (“GnRH”, also known as Luteinizing Hormone Releasing Hormone, or “LHRH”), is of importance to the regulation of fertility. Johnson M., Everitt B. Essential Reproduction, 3rd Edn. Blackwell Scientific Publications, 1988. The gonadotropin hormonal cascade can be halted by neutralization of the biological activity of GnRH. Fraser H. M. Physiological Effects of Antibody to Leutenizing Hormone Releasing Hormone.
In: Physiological Effects of Immunity Against Reproductive Hormones, Edwards and Johnson, Eds. Cambridge University Press, 1976. The use of antibodies to neutralize GnRH has been described as an effective means of contraception. See, U.S. Pat. No. 6,303,123. The scientific and patent literature has described inducing these antibodies by active immunization with GnRH immunogens or by passive immunization by administering anti-GnRH antibodies. Fraser H. M. Physiological Effects of Antibody to Leutenizing Hormone Releasing Hormone.In: Physiological Effects of Immunity Against Reproductive Hormones, Edwards and Johnson, Eds. Cambridge University Press, 1976. Since anti-GnRH antibodies can neutralize the biological activity of GnRH, immunization constitutes an important approach towards treating diseases dependent upon gonadal steroids and other reproductive hormones as well as a means to regulate mammalian fertility.
GnRH has the same amino acid sequence in all mammals (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-GlyNH2) (SEQ ID NO: 1); thus, it has been reported that a single immunogen would be effective in all mammalian species, including humans. However, attempts to induce antibodies or deliver anti-GnRH have been ineffective or have required repeated administration, which is impractical.
There is a good deal of literature describing the ability of antibodies targeting GnRH to safely and effectively inhibit reproductive function in many mammalian species, including rodents [Proc. Natl. Acad. Sci. (1985) 82, 1228-1231], cats [Journal of Reproductive Immunology (2004) 64, 107-119] and dogs [PNAS, cited above; Vaccine (2007) 25, 7111-7119]. Attempts to translate this observation into a useful means of nonsurgical sterilization, however, have been hampered by limitations in the currently available strategies for eliciting an effective antibody response to GnRH. GnRH vaccines have been developed using a wide array of adjuvants and carrier proteins, and some of these have even seen limited use in livestock and domestic animals [Clin. Microbiol. Rev. (2007) 20, 489-510]. Despite the promise of this approach, widespread utilization has been prevented by inconsistency in the induction and maintenance of the humoral immune response to GnRH, even after multiple immunizations Alternatively, passive immunization via direct administration of a neutralizing monoclonal antibody to GnRH has been shown to reliably suppress GnRH activity, but has not represented a practical option for sterilization given the need for repeated antibody administration.
What is needed is a practical, non-surgical veterinary method for neutering and castration of non-human animals.